Epothilones A and B are naturally-occurring compounds that were discovered by Höfle et al. as isolated from fermentation products of the microorganism, Sorangium cellulosum (see, e.g., WO 93/10121). Höfle et al. also discovered 37 natural epothilone variants and related compounds produced by Sorangium cellulosum, including epothilones C, D, E, F and other isomers and variants. See, e.g., U.S. Pat. No. 6,624,310.
Epothilones A and B are major metabolites of Sorangium cellulosum and as natural products, have the following stereospecific forms:

Various derivatives and analogs of the naturally-occurring epothilones have been discovered at Bristol-Myers Squibb Company. Examples of such epothilone analogs include the aza-epothilone B analog known as ixabepilone and aziridinyl-epothilone analogs. See, e.g., U.S. Pat. Nos. 6,605,599; 6,262,094; 6,399,638; 6,498,257; 6,380,395; and 6,800,653.
Certain aziridinyl-epothilone have been discovered as especially useful in preparing compositions for targeted drug therapies in treating cancer, as disclosed in U.S. provisional application Ser. No. 60/808,366, filed May 25, 2006, and U.S. patent application Ser. No. 11/735,785, titled “Azirdinyl-Epothilone Compounds,” (US2007/0276018A1, published 29 Nov. 2007) claiming priority to the 60/808,366 application, assigned to the present assignee, which is hereby incorporated by reference.
Processes for making aziridinyl-epothilone analogs from oxiranyl epothilones are disclosed in U.S. Pat. No. 6,291,684 to Borzilleri et al., and assigned to the present assignee. In Borzilleri, aziridinyl-epothilones are prepared from compounds having stereoconfigurations aligned with epothilones A or B. With these stereospecific compounds, several steps are then taken to make the aziridinyl-epothilones, including breaking the epoxide ring upon reaction with a metal halide, converting the halide to an azide upon reaction with an azide salt, conducting a Mitsunobu reaction to form an intermediate ester, cleaving the ester to form an intermediate azidoalcohol, and then cyclizing the azidoalcohol to provide the aziridinyl-epothilone compounds. See, e.g., U.S. Pat. No. 6,291,684 B1, cols. 2-3. Reportedly, this multi-step process is used to obtain aziridinyl-epothilone compounds retaining the stereoconfiguration of the starting materials. (Col. 1, 1. 57-60).
In Regueiro-Ren et al., Organic Letters, 3:2693-2696 (2001), there is disclosed a scheme for making aziridinyl-epothilones via an intermediate diastereomeric epothilone A, or epi-epothilone A (“epi-epo A”). Regueiro-Ren et al. report the following Scheme:

Regueiro-Ren et al state that epoxidation of 3 gave the desired 12β,13β-epoxide 5 (epi-epo A) but in a ratio of epothilone A to 12β,13β-epothilone A of 3:1. Regueiro-Ren et al. further report that attempts to alter and improve this ratio in favor of the desired 12β,13β-epoxide 5 were unsuccessful, and that other reaction conditions including low temperature, solvent variation, and alternative dioxirane source had no effect on the diastereoselectivity. Regueiro-Ren et al. at page 2694, footnote 8.
Accordingly, there is presented the technical problem of developing efficient processes for making epothilones and analogs, for example, for making epi-epothilones such as epi-epo A or epi-epo B with improved ratios of the epi-stereospecific forms, and for making epothilone analogs such as azirdinyl-epothilone analogs using the epi-epothilones as intermediates.